Throughout this application, citations for various publications are provided in the text. The disclosures of these publications are hereby incorporated in their entirety by reference into this application in order to more fully describe the state of the art to which this invention pertains.
This invention relates to the field of allylic amination. More particularly, the invention relates to a simple procedure for directly preparing allylic amines from allylic compounds.
The subject invention provides a simple, efficient and inexpensive procedure for introducing an amino functionality into the allylic position of alkenes. The procedure is related to one developed by Kresze, et al. (Kresze, G., Munsterer, H., J. Org. Chem. 1983, 48, 3561). The subject invention shows how N,N'-bis-(alkoxy-carbonyl)sulfur diimides can be prepared easily, and how to overcome the large variability in yields of alkyl N-sulfinylcarbamates obtained when alkyl carbamates are combined with thionyl chloride in pyridine.
The problem considered is that while N,N'-bis(methoxycarbonyl)sulfur diimide (1) has considerable benefit as a reagent to effect allylic aminations, e.g. FIG. 3 (Kresze, G., Munsterer, H., J. Org. Chem. 1983, 48, 3561), its preparation (FIG. 1), which calls for the manipulation of chlorine in both steps, is troublesome. Kresze, G., Braxmeier, H., Munsterer, H., Organic Synthesis; Wiley: New York, 1993; Collect. Vol. 8, p 427; Levchenko, E. S., Ballon, Ya, G., Kirsanov, A. V., J. Org. Chem. USSR (Engl. Transl.) 1967, 3, 2014. Thus, if diimide 1 could be obtained more easily, its usefulness for synthesis would increase significantly. The benefit of the scheme shown in FIG. 3 is the facility with which aqueous base removes residual groups from the nitrogen that is introduced, an advantage shared with a more lengthy procedure of Whitesell and Yaser that uses N-sulfinylcarbamates (Whitesell, J. K., Yaser, H. K., J. Am. Chem. Soc. 1991, 113, 3526) but not with those that effect allylic aminations by using reagents such as TsN.dbd.Se.dbd.NTs (Sharpless, K. B., Hori, T., Truesdale, L. K., Dietrich, C. O., J. Am. Chem. Soc. 1976, 98, 269), TsN.dbd.S.dbd.NTs (Sharpless, K. B., Hori, T., J. Org. Chem. 1976, 41, 176; Singer, S. P., Sharpless, K. B., J. Org. Chem. 1978, 43, 1448), PhSO.sub.2 NSO (Deleris, G., Dunogues, J., Gadras, A., Tetrahedron, 1988, 44, 4243), CH.sub.3 --OCON.dbd.NCOOCH.sub.3 plus SnCl.sub.4 (Brimble, M. A. Heathcock, C. H., J. Org. Chem. 1993, 58, 5261), AcNO (Keck, G. E., Webb, R. B., Yates, J. B., Tetrahedron, 1981, 37, 4007), and PhNHOH combined with transition-metal catalysts. (For example, see, Johannsen, M., J.o slashed.rgensen, K. A., J. Org. Chem. 1994, 59, 214.) The leaving groups attached to nitrogen (ArSO.sub.2, NHCO.sub.2 CH.sub.3 or OH plus either Ac or Ph) are not readily removed by hydrolysis.
The amination method disclosed herein is useful for the preparation of biologically active allylic amines. An important application includes the synthesIs of certain allylic amine inhibitors of squalene epoxidase, which have powerful antifungal properties, and are useful in combatting fungal infections. Petraniy, G., Ryder, N. S., Stutz, A., Science (Washington, D.C.), 224, 1239 (1984). Accordingly, the subject method provides a route to prepare SF86-327, a powerful inhibitor of fungal squalene epoxidase. Petraniy, supra.